Behavioral and Neural Mechanisms of Serotonin Modulation of Impulsivity and Reward

Despite its prevalence in many psychiatric disorders, such as attention deficit hyperactivity disorder, suicidal depression, schizophrenia, and aggression and motivational disorders, impulsivity and its biological bases remain poorly understood. Subdivisions of impulsivity, including impulsive action (reduced response inhibition) and impulsive choice (reduced delay of gratification), sometimes present in an uncorrelated manner. This complexity renders pathological impulsivity difficult to treat, as different underlying causes likely result in different phenotypic presentations, despite being placed under one umbrella term. In order to study the behavior and biology of one particular facet of impulsivity, this dissertation utilizes the serotonin 1B receptor (5-HT1BR; an inhibitory G-protein coupled receptor) knockout mouse model, which presents with a specific elevation in impulsive action but not impulsive choice. In Chapter 1, I show that mice lacking the 5-HT1BR have increased impulsive action accompanied by enhanced motivation and responsiveness to palatable rewards, indicating that they may have dysregulation of subjective reward valuation. In Chapter 2, I then explore the 5- HT1BR knockout model from the perspective of behavioral inhibition, demonstrating that knockout mice have intact inhibitory learning despite having difficulty withhold responding for reward. Of particular interest to this particular presentation of impulsive action, therefore, is serotonin neuromodulation of reward circuitry in the brain. In Chapter 3, I first show behaviorally that normalizing reward value in 5-HT1BR knockout mice reduces impulsive action to the level of controls. Neurally, I then complete a series of experiments with targeted knockouts in reward-related brain regions, specifically projections to and from the nucleus accumbens shell, in addition to combined 5-HT1BR genetic heteroreceptor and viral autoreceptor knockout. Only combined Emx1+ heteroreceptor and autoreceptor knockout results in increased motivation and impulsivity similar to the whole brain knockout. On the other hand, combined VGAT+ heteroreceptor and autoreceptor knockout increases hedonic taste reactvity. This suggests that modified serotonin release in addition to multiple 5-HT1B heteroreceptor population losses synergistically modulate neural signaling to increase reward valuation and impulsive action. Together, these studies provide insight into the behavioral and biological bases of impulsive action and propose a framework for better understanding specific presentations of impulsivity

The impact of a computer based adult literacy program on literacy and numeracy : evidence from India

With over 700 million illiterate adults in the world, many governments have implemented adult literacy programs across the world, although typically with low rates of success partly because the quality of teaching is low. One solution may lie in the standardization of teaching provided by computer-aided instruction. We present the first rigorous evidence of the effectiveness of a computer-based adult literacy program. A randomized control trial study of TARA Akshar Plus, an Indian adult literacy program, was implemented in the state of Uttar Pradesh in India. We find large, significant impacts of this computer-aided program on literacy and numeracy outcomes. We compare the improvement in learning to that of other traditional adult literacy programs and conclude that TARA Akshar Plus is effective in increasing literacy and numeracy for illiterate adult women

A Cenozoic-style scenario for the end-Ordovician glaciation

The end-Ordovician was an enigmatic interval in the Phanerozoic, known for massive glaciation potentially at elevated CO2 levels, biogeochemical cycle disruptions recorded as large isotope anomalies and a devastating extinction event. Ice-sheet volumes claimed to be twice those of the Last Glacial Maximum paradoxically coincided with oceans as warm as today. Here we argue that some of these remarkable claims arise from undersampling of incomplete geological sections that led to apparent temporal correlations within the relatively coarse resolution capability of Palaeozoic biochronostratigraphy. We examine exceptionally complete sedimentary records from two, low and high, palaeolatitude settings. Their correlation framework reveals a Cenozoic-style scenario including three main glacial cycles and higher-order phenomena. This necessitates revision of mechanisms for the end-Ordovician events, as the first extinction is tied to an early phase of melting, not to initial cooling, and the largest δ13C excursion occurs during final deglaciation, not at the glacial apex

Aerodynamic study of a tricycle wheel subsystem for drag reduction

This paper deals with a computational fluid dynamics (CFD) and experimental drag analysis on an isolated rotating wheel subsystem (including its accessories: tire, suspension, A-arms, and fender) of a motor tricycle vehicle with two wheels in front. The main goal of the present work is to study the effect of the fender on the wheel subsystem drag and its optimization. The Star CCM+ commercial code was used for the numerical simulations. Different flow conditions were simulated and some results were validated by comparison to wind tunnel experimental results. To perform drag optimization, several aerodynamic fender shapes were designed and simulated as part of the subsystem. A drastic drag reduction up to 30.6% compared to the original wheel subsystem was achieved through numerical simulations

Single-step production of autologous bovine platelet concentrate for clinical applications in cattle.

Platelet concentrate (PC) is an alternative therapy to treat mastitis in dairy cattle and is an alternative treatment for reproduction problems such as endometritis. Unfortunately, double-centrifugation processing methods described are time-consuming, require specialized laboratory equipment, and are usually done in a heterologous way, which risks herd health. To overcome this limitation, we evaluated single-step bovine PC processing methods readily applicable to a farm setting using an autologous conditioned plasma (ACP) production system. We investigated the hematologic findings, cytokines, and growth factors of the obtained PC samples. Autologous conditioned plasma was prepared using whole blood (WB) from 4 cows (group 1) using single-step centrifugation and 16 different processing methods. The 2 protocols that yielded the highest ratio of platelet to white blood cell (WBC) concentration were ACP-1 [720 × g (2,200 rpm), 5 min] and ACP-2 [929 × g (2,500 rpm), 3 min]. They were subsequently reproduced and compared using WB from 8 cows (group 2). Hematologic findings were quantified, IL-1β (cytokine) and growth factors [platelet-derived growth factor (PDGF), transforming growth factor (TGF)-β, bovine fibroblast growth factor (b-FGF)] were measured, and enrichment factors were compared between samples and processing methods. Hematological characteristics and platelet enrichment varied markedly among tested protocols and all were statistically different from WB. Protocol ACP-2 resulted in significantly greater platelet enrichment (mean 169% of WB) than ACP-1 (125% of WB). We found no significant difference between the 2 ACP preparation protocols with regard to leukocyte reduction (7.53-9.75% WBC compared with WB) or growth factor enrichment (124-125% PDGF, 95-100% TGF-β, 102-104% b-FGF, and 56-74% IL-1β compared with WB). In conclusion, both ACP protocols yielded a platelet concentration shown to promote healing for clinical applications in cattle, and the ACP-2 protocol resulted in a greater degree of platelet enrichment. Therefore, this protocol could be used for ACP production for clinical applications in cattle

The impact of a computer-based adult literacy program on literacy and numeracy: Evidence from India

With over 700 million illiterate adults worldwide, governments in many developing countries have implemented adult literacy programs. Typically these programs have low rates of success partly because the quality of teaching is heterogeneous. Standardization of teaching provided by computer-aided instruction might be a solution. However, there is little rigorous evidence of the effectiveness of computer-based adult literacy programs in delivering high-quality literacy and numeracy in the developing world. To fill this void in the literature, we study the impact of a computer-based adult literacy program, Tara Akshar Plus, on the literacy and numeracy skills of previously illiterate adult women in the north Indian state of Uttar Pradesh. Through a randomized control trial, we measure learning outcomes with individual-level literacy and numeracy tests and find statistically significant positive impacts of this computer-aided program on literacy and numeracy outcomes of women who undergo the TARA Akshar Plus program—relative to the control group. The effects are statistically significant but small in magnitude for women who were entirely illiterate prior to the program. The learning impacts are substantially larger for learners who knew at least a handful of letters at the beginning of the program. We compare the improvement in learning to that of another adult literacy and numeracy program. We conclude that TARA Akshar Plus is the more effective of the two, but the literacy and numeracy level achieved are not large enough to make many entirely illiterate learners become functionally literate

Infants’ intentionally communicative vocalisations elicit responses from caregivers and are the best predictors of the transition to language: a longitudinal investigation of infants’ vocalisations, gestures, and word production

What aspects of infants’ prelinguistic communication are most valuable for learning to speak, and why? We test whether early vocalisations and gestures drive the transition to word use because, in addition to indicating motoric readiness, they 1) are early instances of intentional communication and 2) elicit verbal responses from caregivers. In study 1, 11-month-olds (N = 134) were observed to coordinate vocalisations and gestures with gaze to their caregiver’s face at above chance rates, indicating that they are plausibly intentionally communicative. Study 2 tested whether those infant communicative acts that were gaze-coordinated best predicted later expressive vocabulary. We report a novel procedure for predicting vocabulary via multi-model inference over a comprehensive set of infant behaviours produced at 11- and 12-months (n = 58). This makes it possible to establish the relative predictive value of different behaviours that are hierarchically organised by level of granularity. Gaze-coordinated vocalisations were the most valuable predictors of expressive vocabulary size up to 24 months. Study 3 established that caregivers were more likely to respond to gaze-coordinated behaviours. Moreover, the dyadic combination of infant gaze-coordinated vocalisation and caregiver response was by far the best predictor of later vocabulary size. We conclude that practice with prelinguistic intentional communication facilitates the leap to symbol use. Learning is optimised when caregivers respond to intentional vocalisations with appropriate language

Assay of aminoglycosides is influenced by tissue homogenization technique

Recovery of neomycin from tissue homogenates was lower when glass/glass homogenizers were used due to the abrasion of glass which will bind to the drug. Glass homogenizers should be avoided for the determination of aminoglycoside levels in tissues.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42733/1/18_2005_Article_BF01948411.pd

Career success: the role of teenage career aspirations, ambition value and gender in predicting adult social status and earnings

Links between family social background, teenage career aspirations, educational performance and adult social status attainment are well documented. Using a contextual developmental framework, this article extends previous research by examining the role of gender and teenage ambition value in shaping social status attainment and earnings in adulthood. Drawing on data from an 18-year British follow up study we tested a path model linking family background factors (such as family social status and parental aspirations) and individual agency factors in adolescence (in particular, career aspirations and ambition value) to social status attainment and earnings in adulthood. The findings suggest that ambition value is linked to adult earnings. That is, young people for whom it is important to get on in their job earn more money in adulthood than their less ambitious peers. The findings also confirm that teenage career aspirations are linked to adult social status attainment, and suggest that family background factors, teenage career aspirations and ambition value interact to influence social status attainment and earnings in adulthood. Gender differences are discusse